The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Lifestyle information and commercial weight management groups to support maternal postnatal weight management and positive lifestyle behaviour: the SWAN feasibility randomised controlled trial.

OBJECTIVES: To assess feasibility of a future randomised controlled trial (RCT) of clinical and cost-effectiveness of lifestyle information and commercial weight management groups to support postnatal weight management to 12 months post-birth. DESIGN: Two-arm feasibility trial, with nested mixed-methods process evaluation. SETTING: Inner-city unit, south England. POPULATION: Women with body mass indices (BMIs) ≥25 kg/m2 at pregnancy booking or normal BMIs (18.5-24.9 kg/m2 ) identified with excessive gestational weight gain at 36 weeks of gestation. METHODS: Randomised to standard care plus commercial weight management sessions commencing 8-16 weeks postnatally or standard care only. MAIN OUTCOMES: Feasibility outcomes included assessment of recruitment, retention, acceptability and economic data collation. Primary and secondary end points included difference between groups in weight 12 months postnatally compared with booking (proposed primary outcome for a future trial), diet, physical activity, smoking, alcohol, mental health, infant feeding, NHS resource use. RESULTS: In all, 193 women were randomised: 98 intervention and 95 control; only four women had excessive gestational weight gain. A slightly greater weight change was found among intervention women at 12 months, with greatest benefit. Among women attending ten or more weight management sessions. There was >80% follow up to 12 months, low risk of contamination and no group differences in trial completion. CONCLUSION: It was feasible to recruit and retain women with BMIs ≥25 kg/m2 to an intervention to support postnatal weight management; identification of excessive gestational weight gain requires consideration. Economic modelling could inform out-of-trial costs and benefits in a future trial. A definitive trial is an important next step. TWEETABLE ABSTRACT: A feasibility RCT of postnatal weight support showed women with BMIs ≥25 kg/m2 can be recruited and followed to 12 months postnatally.

POPPIE: protocol for a randomised controlled pilot trial of continuity of midwifery care for women at increased risk of preterm birth.

BACKGROUND: High rates of preterm births remain a UK public health concern. Preterm birth is a major determinant of adverse infant and longer-term outcomes, including survival, quality of life, psychosocial effects on the family and health care costs. We aim to test whether a model of care combining continuity of midwife care with rapid referral to a specialist obstetric clinic throughout pregnancy, intrapartum and the postpartum period is feasible and improves experience and outcomes for women at increased risk of preterm birth. METHODS: This pilot, hybrid, type 2 randomised controlled implementation trial will recruit 350 pregnant women at increased risk of preterm birth to a midwifery continuity of care intervention or standard care. The intervention will be provided from recruitment (antenatal), labour, birth and the postnatal period, in hospital and community settings and in collaboration with specialist obstetric clinic care, when required. Standard care will be the current maternity care provision by NHS midwives and obstetricians at the study site. Participants will be followed up until 6-8 weeks postpartum. The composite primary outcome is the appropriate initiation of any specified interventions related to the prevention and/or management of preterm labour and birth. Secondary outcomes are related to: recruitment and attrition rates; implementation; acceptability to women, health care professionals and stakeholders; health in pregnancy and other complications; intrapartum outcomes; maternal and neonatal postnatal outcomes; psycho-social health; quality of care; women's experiences and health economic analysis. The trial has 80% power to detect a 15% increase in the rate of appropriate interventions (40 to 55%). The analysis will be by 'intention to treat' analysis. DISCUSSION: Little is known about the underlying reasons why and how models of midwifery continuity of care are associated with fewer preterm births, better maternal and infant outcomes and more positive experiences; nor how these models of care can be implemented successfully in the health services. This will be the first study to provide direct evidence regarding the effectiveness, implementation and evaluation of a midwifery continuity of care model and rapid access to specialist obstetric services for women at increased risk of preterm birth. TRIAL REGISTRATION: ISRCTN37733900 . Retrospectively registered on 21 August 2017.

Factors influencing attendance at structured education for Type 1 diabetes in south London.

AIM: To investigate the factors influencing uptake of structured education for people with Type 1 diabetes in our local population in order to understand why such uptake is low. METHODS: We conducted a cross-sectional database study of adults with Type 1 diabetes in two south London boroughs, analysed according to Dose Adjustment For Normal Eating (DAFNE) attendance or non-attendance. Demographics, glycaemic control and service use, with subset analysis by ethnicity, were compared using univariate analysis. An exploratory regression model was used to identify influencing factors. RESULTS: The analysis showed that 73% of adults had not attended the DAFNE programme. For non-attenders vs attenders, male gender (59 vs 48%; P = 0.002), older age (39 vs 35 years; P < 0.001), non-white ethnicity (30 vs 20%; P = 0.001) and coming from an area of social deprivation (index of multiple deprivation score 31 vs 28; P < 0.001) were associated with non-attendance. The difference in gender (88% men vs 70% women; P < 0.001) and age (43 vs 34 years) persisted in the non-white group. Regression analysis showed that higher baseline HbA1c level (odds ratio 1.96; P = 0.004), younger age (odds ratio 0.98; P = 0.001) and lower social deprivation (odds ratio 0.52; P = 0.001) was associated with attendance. CONCLUSION: Socio-economic status and factors perceived as indicating greater severity of disease (HbA1c ) influence attendance at DAFNE. More work is necessary to understand the demography of non-attenders to aid future service design and alternative engagement strategies for these groups.

Spontaneous spinal epidural haematoma mimicking meningitis in a 2-year-old child--a case report and literature review.

INTRODUCTION: We report the case of a 2-year-old boy with suspected meningitis who presented with acute onset neck pain and stiffness associated with right-sided weakness and ataxia. MANAGEMENT: Despite intravenous antibiotics and antiviral treatment, his condition deteriorated. Magnetic resonance imaging demonstrated spontaneous cervical epidural haematoma (C4-C7) extending down to thoracic (T7) level with associated compression of the spinal cord. He was treated successfully by neurosurgical decompression and made a complete recovery. DISCUSSION: Spinal epidural haematoma is a neurosurgical emergency characterised by extravasation of blood in the spinal epidural space. The clinical presentation particularly in young children can masquerade other conditions such as meningitis. In this article, we discuss our case and review the literature on spontaneous spinal epidural hematoma with an aim to improve awareness of this condition which if not recognised and treated early can lead to significant lifelong morbidity.

Off label use of devices and drugs in interventional radiology.

AIM: To establish how often off-label device and drug use occurs in interventional radiology (IR) in a UK tertiary referral hospital and consider the wider implications for the interventional radiologist. MATERIALS AND METHODS: Prospective data were collected during interventional procedures for 1 working week in a university hospital. Out-of-hours procedures and procedures outside the department were excluded. Operators were asked to record the drugs and devices used, the indication, and method of use. The instructions for use/summary of product characteristics were then studied for each device/drug used to assess if the use was on or off-label. RESULTS: During the study period 52 cases were performed and data were available on 26 cases (50%). In 22 of the 26 cases (84%) there was evidence of off-label use of devices or drugs. Off-label use of drugs included treatment of venous malformations with Fibrovein(©) (sodium tetradecyl sulphate), which is licensed for the treatment of varicose veins in the leg, and intra-arterial injection of heparin, which is licensed for intravenous and subcutaneous use. Off-label device use included placing vascular sheaths in the urinary tract, using angiographic catheters to guide wires in the urinary tract, using sheaths for thrombosuction, reshaping of the tip of most guidewires, and using angioplasty balloons to dislodge the arterial plug at fistula thrombectomy. CONCLUSION: Off-label device and drugs use is common in a UK tertiary hospital IR department and literature suggests this is common in the wider IR community. There are important clinical and legal implications for off-label use for patients and physicians.

Treatment of a branchial sinus tract by sclerotherapy.

A 16-year-old female presented with a sinus on the skin just medial to the right clavicle, which had discharged clear fluid on a daily basis for a number of years. A sinogram was performed and showed a long sinus tract extending from the region of the right clavicle to the lateral pharyngeal wall. Surgical treatment would have required an extensive procedure and seemed inappropriate in view of the relatively mild symptoms the patient was experiencing. Instead sclerotherapy was used to induce healing of the lesion. This was performed using 3% sodium tetradecyl sulphate foam delivered via a catheter along the entire length of the tract. There were no immediate complications from this procedure and on review at 1 and 6 weeks post-procedure the patient reported a significant improvement in the fluid discharge. At 1 year post-procedure this improvement had been sustained. The patient did report an occasional discharge from the sinus tract orifice at the base of her neck, but she did not feel that this was a significant problem and declined any further treatment.

Clinical and instrumental parameters in patients with constipation and incontinence: their potential implications in the functional aspects of these disorders.

PURPOSE: The aims of this study were to evaluate several clinical and instrumental parameters in a large number of patients with constipation and incontinence as well as in healthy controls and discuss their potential implications in the functional aspects of these disorders. METHODS: Eighty-four constipated and 38 incontinent patients and 45 healthy controls were submitted to a protocol based on proctologic examination, clinico-physiatric assessment, and instrumental evaluation. RESULTS: Constipated and incontinent patients had significantly worse lumbar lordosis as well as lower rate in the presence of perineal defense reflex than controls. Constipated but not incontinent patients had a lower rate of puborectalis relaxation than controls. Furthermore, worse pubococcygeal tests and a higher rate of muscle synergies presence, either agonist or antagonist, were observed in both constipated and incontinent patients compared to controls. CONCLUSIONS: This study has demonstrated strong correlations between physiatric disorders and the symptoms of constipation and incontinence. Further studies designed to demonstrate a causal relationship between these parameters and the success of a specific treatment of the physiatric disorders on the proctology symptoms are warranted.

Feedback from incident reporting: information and action to improve patient safety.

INTRODUCTION: Effective feedback from incident reporting systems in healthcare is essential if organisations are to learn from failures in the delivery of care. Despite the wide-scale development and implementation of incident reporting in healthcare, studies in the UK suggest that information concerning system vulnerabilities could be better applied to improve operational safety within organisations. In this article, the findings and implications of research to identify forms of effective feedback from incident reporting are discussed, to promote best practices in this area. METHODS: The research comprised a mixed methods review to investigate mechanisms of effective feedback for healthcare, drawing upon experience within established reporting programmes in high-risk industry and transport domains. Systematic searches of published literature were undertaken, and 23 case studies describing incident reporting programmes with feedback were identified for analysis from the international healthcare literature. Semistructured interviews were undertaken with 19 subject matter experts across a range of domains, including: civil aviation, maritime, energy, rail, offshore production and healthcare. RESULTS: In analysis, qualitative information from several sources was synthesised into practical requirements for developing effective feedback in healthcare. Both action and information feedback mechanisms were identified, serving safety awareness, improvement and motivational functions. The provision of actionable feedback that visibly improved systems was highlighted as important in promoting future reporting. Fifteen requirements for the design of effective feedback systems were identified, concerning: the role of leadership, the credibility and content of information, effective dissemination channels, the capacity for rapid action and the need for feedback at all levels of the organisation, among others. Above all, the safety-feedback cycle must be closed by ensuring that reporting, analysis and investigation result in timely corrective actions that effectively address vulnerabilities in existing work systems. CONCLUSIONS: Limited research evidence exists concerning the issue of effective forms of safety feedback within healthcare. Much valuable operational knowledge resides in safety management communities within high-risk industries. Multiple means of feeding back recommended actions and safety information may be usefully employed to promote safety awareness, improve clinical processes and promote future reporting. Further work is needed to establish best practices for feedback systems in healthcare that effectively close the safety loop.

A preliminary investigation of the reliability and validity of the Brief Assessment Schedule Depression Cards and the Beck Depression Inventory-Fast Screen to screen for depression in older stroke survivors.

OBJECTIVE: To conduct an initial assessment of the reliability and validity of the Brief Assessment Schedule Depression Cards (BASDEC) and the Beck Depression Inventory-Fast Screen (BDI-FS) to screen for depression in older stroke survivors. METHODS: Participants from four inpatient rehabilitation units completed the BASDEC and the BDI-FS together with the Hospital Anxiety and Depression Scale (HADS) for comparison. The Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID) was then completed with all participants to ascertain a criterion depression diagnosis. The BASDEC and BDI-FS were subsequently completed for a second time. RESULTS: Forty-nine stroke survivors (M=78.80, SD=6.79 years) were included. The BASDEC and BDI-FS demonstrated acceptable internal consistency and test-retest reliability. The BASDEC (cut-off >or=7) resulted in a sensitivity of 1.0 and specificity of 0.95 for detecting major depression whereas the BDI-FS (cut-off >or=4) had a sensitivity of 0.71 and specificity of 0.74. When participants with minor depression were included in analyses, sensitivity lowered to 0.69 (specificity=0.97) for the BASDEC and 0.62 (specificity=0.78) for the BDI-FS. CONCLUSIONS: The BASDEC and BDI-FS were found to have acceptable reliability. The BASDEC demonstrated some advantage in criterion validity over the BDI-FS at the examined cut-offs.

Quantifying distraction and interruption in urological surgery.

BACKGROUND: To enhance safety in surgery, it is necessary to develop a variety of tools for measuring and evaluating the system of work. One important consideration for safety in any high-risk work is the frequency and effect of distraction and interruption. AIM: To quantify distraction and interruption to the sterile surgical team in urology. METHODS: Observation of the behaviour of the surgical team and their task activity determined distraction and interruption recorded. Using an ordinal scale, an observer rated each salient distraction or interruption observed in relation to the team's involvement. RESULTS: The frequency of events and their attached ratings were high, deriving from varying degrees of equipment, procedure and environment problems, telephones, bleepers and conversations. DISCUSSION: With further refinement and testing, this method may be useful for distinguishing ordinal levels of work interference in surgery and helpful in raising awareness of its origin for postoperative surgical team debriefing.

Defining the technical skills of teamwork in surgery.

Developments in surgical technology and procedure have accelerated and altered the work carried out in the operating theatre/room, but team modelling and training have not co-evolved. Evidence suggests that team structure and role allocation are sometimes unclear and contentious, and coordination and communication are not fully effective. To improve teamwork, clinicians need models that specify team resources, structure, process and tasks. They also need measures to assess performance and methods to train teamwork strategically. An effective training strategy might be to incorporate teamwork with other technical skills training in simulation. However, the measures employed for enhancing teamwork in training and practice will need to vary in their object of analysis, level of technical specificity, and system scope.

Simulators in catheter-based interventional radiology: training or computer games?

Training in interventional radiology (IR) relies on a traditional apprenticeship; to protect patients, expert supervision is mandatory until knowledge, attitudes and practical skills have been certified as satisfactory. However, the current quality of IR training is threatened by reduced time for trainees to learn, as well as a loss of basic diagnostic, training cases to non-invasive imaging. At the same time, IR techniques are becoming a focus of interest to a range of other clinical specialities. To address this training shortfall there is a need to develop novel training alternatives such as simulator models. Few simulator models in any medical field have been successfully validated to show improved clinical skills in treating patients. To date no endovascular simulator has met this standard. A good simulator must be based around key performance measures (metrics) derived from careful analysis of the procedure to be replicated. Metrics can be determined by trained psychologists from a direct analysis of the content of the job or task to be tested. The identification of these critical measures of performance is a complex process which must be tailored to a training curriculum to be effective. Simulators based on flawed metrics will invariably lead to unsatisfactory assessment. It follows that simulator development must involve the statutory licensing authorities. Equally it is essential that we do not assume that training on a particular simulator will correlate with the ability to perform the task in the real world. This "transfer of training" must be rigorously proven by validation studies.

Measuring intra-operative interference from distraction and interruption observed in the operating theatre.

An observational tool was developed to record distraction and interruption in the operating theatre during surgery. Observed events were assigned to pre-defined categories and rated in relation to the level of team involvement - the sum of which was treated as a measure of intra-operative interference. Many events (0.29 +/- 0.02 per min) were observed and rated in 50 general operations sampled from a single operating theatre. The rating of individual events (r(s) = 0.65) and of cases (r(s) = 0.89) correlated between independent observers. Interference levels (1.04 +/- 0.07/min) also correlated with door opening frequency (0.68 +/- 0.03/min) (r = 0.47, p < 0.001). Some sources of interference were intrinsic to the work of the surgical team, including equipment, procedure and environment, while others were extraneous, including bleepers, phone calls and external staff. The findings highlight the need to further develop measures of interference, to assess its variation, intensity and its effect on surgical team performance.